Preparation of alkali metal monoaliphatically substituted amides



Patented Aug. 3, 1954 PREPARATION OF ALKALI METAL MONO- ALIPHATICALLY SUBSTITUTED AMIDES David D. Humphreys, Riverview, Mich., assignor to Sharples Chemicals 1110., a corporation of Delaware No Drawing. Application May 1, 1951, Serial No. 224,047

14 Claims. 1

The present invention pertains to organically substituted amides of the alkali metals, and particularly to such compounds which have one monovalent, aliphatic, hydrocarbon substituent attached to the nitrogen atom, one atom of an alkali metal attached to th nitrogen atom, the third valence of the nitrogen being satisfied by hydrogen. The invention is particularly concerned with a, new and novel process for preparing these alkali metal monoaliphatically substituted amides, said process being outstandingly superior to processes hitherto available for the preparation of such compounds.

Accordingly, a principal object of the invention is to provide a superior method for preparing a quite old class of compounds, namely, alkali metal monoaliphatically substituted amides. Another object is to prepare these products in high yield and purity, so that they can be used to advantage in a wide variety of chemical syntheses, a purpose for which they are eminently suited owing to their tremendous reactivity. These and other objects will be apparent from the following description.

Somesuch compounds, and particularly such potassium and cesium compounds, have been prepared in the past by the direct reaction of primary aliphatic amines and alkali metals, in accordance with Equation 1:

in which R may be an alkyl group for example, and M may be an alkali metal, such as potassium or cesium. At first glance this reaction appears to be quite attractive, for the reactants and products are simple. In actual practice, however, such reactions are difficult to carry out and yields are not satisfactory. Thus it is understandable that reactions of this kind, although first reported many years ago, have attained little favor among chemists.

Somewhat more recently, it has been proposed to prepare compounds such as the compounds of the present invention, by reacting primary aliphatic amines with aikali n'ietallo organic compounds in which the metal is attached to carbon. The difliculties, Well-known to chemists,

of working with such metallo-organic compounds hav militated seriously against the success of such proposals. Furthermore, the use of such intermediate metallo-organic compounds frequently complicates the isolation and/or use of the alkali metal substituted amides by contaminating the desired products with by-products, such as when the metallo-organic compound employed in the reaction is derived from naphthalene, chlorobenzene, amyl chloride, etc.

I have discovered a new process for preparing alkali metal monoaliphatically substituted amides, whereby these products are obtained in high yields and the various disadvantages of the above older processes are avoided.

In the practice of the invention, a primary aliphatic amine is reacted with an alkali metal amide, the reaction being as shown in Equation 2:

wherein M represents an alkali metal such as lithium, sodium, potassium, cesium, or rubidium; and wherein R represents a monovalent aliphatic radical such as alkyl or cycloalkyl. The term cycloalkyl is meant to include not only such unsubstituted radicals, but also such radicals having from 1 to 3 alkyl radicals of from 1 to 5 carbon atoms as substituents on the carbocyclic ring.

My process requires that no large amount of ammonia be present in the reaction zone as the reaction proceeds, it being necessary to remove ammonia from said zone, in order that the reaction may proceed in the desired direction, i. e. to the right in Equation 2 above. Various expedients are available for accomplishing this step, as will be obvious. For convenience, this positive step for removing ammonia from the reaction zone will be referred to by the term stripping ofi ammonia, or its equivalent.

My discovery is most surprising, particularly in view of Fernelius and Watt, Chemical Reviews, volume 20, page 236. According to these authors, alkali metal monoaliphatically substituted amides derived from aliphatic amines are subject to extensive ammonolysis. By means of an illustrative equation, they indicate the irreversible reaction of ammonia with alkali metal monoaliphatically substituted amides, to yield the corresponding unsubstituted metal amides and primary aliphatic amines.

I have also discovered that secondary aliphatic amines do not react with alkali metal amides to produce the corresponding alkali metal disubstituted amides and ammonia. Consequently, such amines are not employed in my new process.

Tertiary aliphatic amines also cannot be employed in my process, owing to the absence of N-attached hydrogen.

It is pointed out that but two products are formed in the practice of the invention, namely, the desired substituted amides, which are solid, and ammonia, which is readily separable therefrom. Purification and isolation problems are thus greatly simplified.

As to the radical R in the foregoing Equation 2, examples of such alkyl radicals are methyl, ethyl, propyl, butyl, amyl, hexyl, heptyl, octyl, nonyl, decyl, undecyl, dodecyl, tridecyl, tetradecyl, pentadecyl hexadecyl, heptadecyl, octadecyl, etc., in cluding the various isomeric forms thereof.

Examples of cycloalkyl radicals are cyclohexyl, methylcyclohexyl, dimethylcyclohexyl, trimethylcyclohexyl, ethylcyclohexyl, propylcyclohexyl, butylcyclohexyl, amylcyclohexyl, methylethylcyclohexyl, ethylamylcyclohexyl, diamylcyclo hexyl, methyldiethylcyclohexyl, etc., including the various isomeric forms thereof. Further examples of such cycloalkyl radicals are cyclopropyl, cyclobutyl, cyclopentyl, cycloheptyl, cyclooctyl, and such radicals having the same number and kind of alkyl substituents as the substituted cyclohexyl radicals just mentioned.

Examples of primary alkylamines which may be employed in my process are methylamine, ethylamine, propylamine, butylamine, amylamine, hexylamine, heptylamine, octylamine, nonylamine, decylamine, undecylamine, dodecylamine, tridecylamine, tetradecylamine, pentadecylamine, hexadecylamine, heptadecylamine, octadecylamine, etc., including the various isomeric forms thereof. Such amines having from 1 to 18 carbon atoms are preferred owing to their more ready availability.

Examples of primary cycloalkylamines which may be employed in my process are cyclohexylamine, methylcyclohexylamine, dimethylcyclohexylamine, trimethylcyclohexylamine, ethylcyclohexylamine, propylcyclohexylamine, butyl cyclohexylamine, amylcyclohexylamine, methylethylcyclohexylamine, ethylamylcyclohexylamine, diamylcyclohexylamine, methyldiethylcyclohexylamine, etc., including the various isomeric forms thereof. amines are cyclopropylamine, cyclobutylamine, cyclopentylamine, cycloheptylamine and cyclooctylamine. Cycloalkylamines having from 3 to 8 carbon atoms and having no ring substitution are generally preferred.

The above reaction between primary aliphatic amines and alkali metal amides is preferably carried out under substantially anhydrous conditions, and preferably employing substantially anhydrous amine reactants, as well as dry inert solvents or diluents in cases where used. Both the unsubstituted alkali metal amide reactants and substituted amide products are highly susceptible to decomposition by water.

Unsubstituted and substituted alkali metal amides are also subject to decomposition by certain substances other than water. Examples of such substances are organic hydroxy compounds such as alcohols, organic halides, and oxygen, and it is preferred that such materials also be evcluded from the reaction system.

It is pointed out that aliphatic alcohols and halides are common contaminants of primary aliphatic amines, owing to the fact that said amines often are manufactured from such compounds. Therefore, when amines so derived are to be employed in my process, such undesirable contaminants should be removed substantially completely. Generally speaking, it is also preferred that no large amount of secondary and/or Other examples of such tertiary amines be present in the primary amines which are used for reaction purposes, for in some instances undesirable side reactions may occur because of their presence.

Accordingly, it is preferred that the reaction be carried out in the substantial absence of substances capable of causing undesired side reactions under the conditions obtaining in the reaction zone.

In a preferred practice of the invention, the alkali metal amide and the primary aliphatic amine which are to be reacted are introduced into a reaction vessel provided with means of efficient agitation and with fractionation equipment suitable for clean-cut separation of ammonia and the amine. Before such introduction, however. the reaction system is dried in any suitable manner, after which it is thoroughly purged with an inert gas such as nitrogen.

It is preferred that the amine employed contain no substantial amounts of contaminants as those contaminants pointed out above.

Since one of the reactants, namely, the alkali metal amide, is present in solid phase during the reaction, it is preferred that said solid be finely divided. Commercial metal amides may be employed if desired; in some instances, further pulverization of such products may be beneficial. Since such commercial amides frequently deteriorate somewhat during storage, generally speak ing it is considered good practice to make certain that the metal amide employed for reaction purposes is freshly prepared and of good purity. A further reason for the use of freshly prepared metal amide is prudence, since there have been reports of explosions which were through to be due to decomposition products formed upon prolonged storage of the amide; see Bergstrom and Fernelius, Chemical Reviews, volume 12, pages 63-65.

The reactants may be employed in stoichiometric amounts, or an excess of either reactant may be employed if desired for any reason. Ordinarily there is no advantage to be gained by the use of an excess of the alkali metal amide.

Usually it is preferred to conduct the reaction in the presence of a solvent or diluent, such as a substantial excess of the primary amine which is being reacted, in order to improve the fluidity of the reaction mass. Except in the case of such primary amine, such solvent or diluent is preferably inert in the sphere of reaction. In this connection it is pointed out that since both the amide reactant and the amide product are solid. fluidity of the reaction mass helps in minimizing deposition of amide product on amide reactant. Such deposition, if it occurs to any considerable extent, retards the reaction. The amide prodnets of the invention have appreciable solubility in primary aliphatic amines. Thus such amines, when employed in excess, serve to a considerable extent as actual solvents rather than as mere diluents.

The amines are of course rather expensive, and it is entirely feasible to employ diluents or other solvents as a means of maintaining a fluid reaction mass. Such diluents should be inert toward the reactants and the products. Liquid saturated aliphatic hydrocarbons, e. g. such hydrocarbons containing from say 6 to 20 carbon atoms or even more, are very suitable.

It is preferred to conduct the reaction with continuous agitation.

When the reaction is carried out in the presence of a solvent or diluent, the desired degree '5 of agitation may be obtained by the use of com ventional mixing equipment such as is used in many chemical syntheses, e. g. simple propellers, high-speed mixers, etc.

On the other hand, when the reactants are brought together in stoichiometric amounts in the absence of a solvent or diluent, special grinding or comminuting equipment is highly useful. It is well to bear in'mind reports that solid a1- kali metal amides, particularly when they contain certain impurities originating during storage, may at times detonate upon mechanical shock, for reasons that are not entirely understood. For these reasons, this particular mode of manufacture is not preferred.

In any event, it is preferred that the reactants be intimately mixed during the course of the reaction.

The reaction is conducted at a temperature sufficiently high to cause the reaction to proceed at a reasonable rate, but sufiiciently low not to lead to any substantial decomposition of reactants and/or products, such as between C. and 158 C., and particularly between C. and 100 C. It is of course understood that the particular reaction temperatures employed will depend to some extent upon the specific reaction system. In general, temperature should be so maintained that separation of ammonia from the amine reactant and the solvent or diluent, is facilitated.

For reasons of convenience, it is often preferred to carry out the process with the exclusion of air and at atmospheric pressure, although at times the use of subatmospheric or superatmospheric pressures preferably may be resorted to, also with the exclusion of air. For example, the use of superatmospheric pressures is often resorted to for preventing loss of such amines as might be volatilizcd under the particular tem perature conditions being employed. On the other hand, the use of subatmospheric pressures is sometimes helpful, as when amines of relatively high molecular weight are being employed as reactants. In such cases, stripping off ammonia from the reaction mass by fractionation of said ammonia from the amine may be accomplished within temperature ranges which are not conducive to decomposition of any component of the reaction system.

It is pointed out that in any event it is preferred that temperature-pressure relationships be such that ammonia is stripped ofl, i. e. by fractional distillation.

As the ammonia is stripped sit and carried away from the reaction system, it may be collected by any convenient means, such as by con densation, or by passage through a water or acid scrubber system, in order to recover said ammonia in free or chemically combined form, as a valuable by-product.

The amount of ammonia recovered during any given period provides an excellent measure of the progress of the reaction. When no significant further quantities of ammonia are being recovered, it can be considered that the reaction is complete. Almost quantitative yields of am monia, and hence of the alkali metal monoaliphatically substituted amide, are commonly obtained.

Because of the great reactivity of these substituted amides, they are utilized to good advantage while still dissolved or suspended in the solvent or diluent in which they are prepared.

. However, the product per se may be isolated if '6 desired according to known methods, such as filtration, crystallization, precipitation, and concentration. During such isolation operations, it isto be understood that precautions preferably should be taken to exclude oxygen, moisture, etc.

As to the alkali metal amides which may be employed in this invention, sodium amide is somewhat preferred in view of its relatively low cost.

Individual alkali metal amides may be used for reaction purposes, or mixtures of different amides may be used if desired. The same is true with respect to the primary aliphatic amines of the invention.

It is pointed out that, generally speaking, a primary amine having the amino group attached to a primary carbon atom reacts more rapidly than an isomeric primary amine having the amino group attached to a secondary carbon atom, which in turn reacts more rapidly than an isomeric primary amine having the amino group attached to a tertiary carbon atom.

If desired, means for removal of ammonia may be employed other than fractionation. For'example, one such means comprises stripping out ammonia by passage of a stream of inert gas, such as nitrogen, through the reaction mixture as the reaction proceeds.

Various other modifications of my invention are possible, and will suggest themselves to persons skilled in the art.

The following examples are given by way of illustration and not of limitation.

EXAMPLE 1 Sodium isopropylaim'dc Twenty-three grains (one gram atom) of sodium was converted into sodium amide according to the procedure described in Inorganic Syntheses, vol. 2, pages 134-5. The apparatus used consisted of a l-liter, 3-neck flask equipped with a Dry-lce-cooled reflux condenser, efficient agitator and suitable inlet tubes for the introduction of liquid ammonia and metallic sodium. After the formation of sodium amide was complete, the excess ammonia was evaporated away and the condenser was replaced with an efficient system for fractional distillation.

Air and traces of ammonia were swept from the system with a stream of dry nitrogen. Next, 500 ml. of purified isopropylamine Was added and the mixture of amine and sodium amide was agitated and heated to the boiling point of the amine. Heating was continued while ammonia was stripped from the system as formed; the amine contained therein being refluxed by virtue of the fractional distillation system. The ammonia thus separated was collected by passage through a scrubber in which a known quan tity of dilute sulfuric acid was being circulated. After 121 hours of heating, 96% of the theoretical ammonia had been collected. The reaction mass was composed of a light grey solid, partially dissolved and partially suspended in a light brown supernatant liquid. This product contained 78 grams of sodium isopropylamide.

EXAMPLE 2 Sodium n-butylamlide In the same apparatus and by the same procedure as described in Example 1, 23 gms. (1 gm. atom) of sodium was converted to sodium amide. Treatment of the sodium amide with 200 ml. of n-butylamine was the same as in Example 1 except that 500 ml. of toluene was used as an inert diluent. Initially, the reaction temperature was 97 C. and after 17% hours of heating, 80.6% of the theoretical yield of ammonia had been recovered and the reaction temperature had risen to l.5 C. After 41 hrs, 89.6% of the theoretical amount of ammonia had-been formed and the reaction temperature was 107 C. The reaction was terminated after 63 hours when 96.3% of the theoretical ammonia had been collected and the reaction temperature was 109 C.

Excess butylamine was distilled from the reaction mass to a vapor temperature of 104 C. and the charge was cooled under an atmosph re of natural gas. The product was a grey solid suspended in a light yellow supernatant liquid. When the reaction mixture had cooled to room temperature, it was filtered under a nitrogen atmosphere. The filter cake was quickly tran., ferred to a tared flask and dried at reduced pressure to yield 70 grams of a tan pyrophoric powder, sodium n-butylamide. This yield would have been higher except for some handling losses caused by the pyrophoric nature of the product.

The powder was analyzed by hydrolyzing a sample weighing 0.8705 gm., distilling the volatile base, and determining the base contained in the distillate by titration with standard acid; nbutylamine found, 0.757 gm. According to these data, the product obtained in the reaction had a purity of 87%.

The base was further identified as n-butyl amine by reacting a sample of the distillate with phenyl isothiocyanate, to obtain l In-butyl-l T- phenylthiourea having a melting point of 63-64 C. A mixture of this product with an authentic specimen of N -n-butyl-N'-phenylthiourea also melted at 63-6? C.

A sample of the above tan powder was shown to have the sodium atom attached to the nitrogen atom of the amine by causing it to react with carbon dioxide. Treatment of the carbonated product with water and phenyl isothiocyahate to yield only N-nbutyl-N'phenylthiourea confirmed that the sodium atom was attached to the nitrogen atom and not to a carbon atom.

EXAMPLE 3 Sodium cyclohexyld'rn dc Percent of theoretical NHa Elapsed time, hrs.

1 Reaction terminated at this point.

The reaction mass. was cooled under a natural gas atmosphere and was filtered under nitrogen. The product was dried as in Example 2 to yield '8 255 gms. of a tan pyrophoric powder, sodium cyclohexylamide.

EXAMPLE 4 Sodium n-ociylamidc In the same apparatus and using the same procedure as in Example 1, 23 gm. of sodium was converted to sodium amide.

A solution of 142 gms. of n-octylamine in 500 ml. of dry hexane was added, and the mixture was heated at its boiling point. As the reaction progressed, the boiling point of the reaction mixture diminished. After 118 hrs. the boiling point had reached a substantially constant value and the reaction was considered complete. The product comprised a light yellow, supernatant liquid (hexane and dissolved sodium n-octylamide) with a small amount of light grey, finely divided powder suspended therein.

EXAM PLE 5 Sodium tert-amy amidc The sodium amide obtained from 23 gm. of sodium was caused to react with 365 gm. (500 ml., 4.19 mole) ofpurified tert-amylamine as in Ex ample 1. After 256 hours, 500 ml. of dry heptane was added to the reaction mixture and 275.4 gins. (3.15 mols) of excess amine was distilled from the reaction mixture. This recovery of unchanged amine indicated a substantially quantitative conversion of sodium amide to sodium tertamylamide. The product was quite soluble in heptane, and was obtained as a tan solid, partially suspended and partially dissolved, in a light brown liquid. As the reaction mass cooled, additional product deposited upon the walls of the vessel as hard, adherent crystalline material.

EXAMPLE 6 Sodium ethylamz'de Sixty-nine grams (3 gm. atoms) of metallic sodium was converted into sodium amide as in Example 1. The resulting sodium amide was transferred to a steel autoclave of two gallon capacity, equipped with a fractionating column bearing a pressure regulating valve, agitator and thermostatically controlled source of heat. The autoclave and fractionating column had been previously cleaned, dried and purged with dry nitrogen. An atmosphere of nitrogen was maintained during transfer of the sodium amide. Next, 1935 gm. of purified ethylainine was added to the autoclave and heating was begun. At a temperature of 78 C. the pressure was 90 lbs./ sq. in. and the pressure regulating valve was slowly passing ammonia of reaction. As the how of ammonia diminished, increasing reactor temperatures were required to maintain constant pressure and a maximum of C. was reached. After thirty hours, virtually no more ammonia was being evolved and the reaction was considered complete. Analysis of the acid scrubber liquid showed a content of 50.9 gm. of ammonia (99.8% of theoretical), thus indicating substantially quantitative yield of sodium ethylarnide. The product was obtained as a solution weighing 1700 gms.

It is to be understood that the more particular description given above is by way of illustraion, and that various modifications are possible and will occur to persons skilled in the art upon becoming familiar herewith. Accordingly, it is intended that the patent shall cover, by suitable expression in its claims, the features of patentable novelty which reside in the invention.

I claim:

1. A process for the preparation of alkali metal monoaliphatically substituted amides having the formula MNHz with a compound having the structure RNHz wherein M and B have the same meanings as above; maintaining substantially anhydrous conditions in the reaction zone and stripping off ammonia from the reaction mass during the reaction.

2. The process of claim 1 in which temperature conditions are maintained between 20 C. and 150 C.

3. The process of claim 1 in which temperature conditions are maintained between 50 C. and 100 C.

4. The process of claim 2 in which M is sodium. 5. The process of claim 4 in which R is an alkyl radical.

6. The process of claim 5 in which R. has 2 carbon atoms.

7. The process of claim 5 in which R has 3 carbon atoms.

8. The process of claim 5 in which R has 4 carbon atoms.

9. The process of claim 5 in which R has 8 carbon atoms.

10. The process of claim 4 in which R is an unsubstituted cycloalkyl radical.

11. The process of claim 10 in which R is the cyclohexyl radical.

12. The process of claim 1 in which the reaction is carried out in the substantial absence of alcohols, organic halides and oxygen.

13. The process of claim 1 in which the reaction is carried out in the substantial absence of alcohols, organic halides, oxygen, secondary amines, and tertiary amines, and in the presence of a stoichiometricexcess of the amine reactant.

14. A process for the preparation of alkali metal monoaliphatically substituted amides which comprises intimately mixing sodium amide with a primary alkyl amine having the amino group attach d to a primary carbon atom of the alkyl radical, said alkyl radical containing from 1 to 18 carbon atoms, maintaining substantially anhydrous conditions in the reaction zone, and as the reaction proceeds stripping ammonia from the reaction mass.

References Cited in the file of this patent Richter: Organic Chem, vol. 1, 3rd ed. (1944), p. 192.

Meunier et al.: Compt. Rendu, vol. 144 (1907), pp. 27345.

Krabbe et al.: Ber. Den. Chem, vol. 743 (1941), pp. 1343-52. 

1. A PROCESS FOR THE PREPARATION OF ALKALI METAL MONOALIPHATICALLY SUBSTITUTED AMIDES HAVING THE FORMULA 